Naloxone, naltrexone and nalbuphine are known, chemically similar drugs and are described in the 1984 USAN and the USP Dictionary of Drug Names, United States Pharmacopiea Convention, Inc., Rockville, MD pp. 327 and 378 (1983). The therapeutic administration of naloxone and nalbuphine is currently limited to injection or infusion typically from solution of the hydrochloride and naltrexone is under investigation for similar administration. Although various types of transdermal therapeutic systems for delivering a wide variety of drugs are known to the art, such as described in U.S. Pat. Nos. 3,598,122, 3,598,123, 4,379,454, 4,286,592, and 4,317,557, (which are all incorporated herein by reference) for example, none of these patents are directed specifically to systems for the transdermal delivery of either naloxone, naltrexone or nalbuphine. We found that the permeability through skin of these drugs is too low to produce any therapeutic effect from a reasonably sized therapeutic system. When we attempted to increase their permeation through skin by the contemporaneous administration of conventional permeation enhancers we were either unsuccessful in increasing the flux or we observed unacceptable levels of irritation to the skin.
According to this invention we have discovered that the base form of naloxone, naltrexone and nalbuphine can be delivered through intact skin at fluxes capable of producing therapeutic effects if delivered in the presence of permeation enhancing amounts of polyethylene glycol monolaurate (PEGML) and have provided drug/permeation enhancer reservoir compositions and transdermal therapeutic systems incorporating the same which are useful in the transdermal delivery of naloxone, naltrexone and nalbuphine.
It is accordingly an object of this invention to provide transdermal therapeutic systems for the delivery of naloxone, naltrexone and nalbuphine through intact skin.
It is another object of this invention to provide drug reservoir/permeation enhancer compositions for use in the transdermal delivery of naloxone, naltrexone and nalbuphine.
It is another object of this invention to provide a method for the transdermal administration of naloxone, naltrexone and nalbuphine.
These and other objects and advantages will be readily apparent from the following description with reference to the accompanying drawings wherein: